Researchers at Childrens Hospital Los Angeles Discover Possible Connection Between Changes in Brain Wiring and Predisposition to Obesity

February 5, 2008

Study suggests that appetite may be hard-wired and that our future weight could be set in the first weeks of life

    LOS ANGELES—Research-scientists at The Saban Research Institute of Childrens Hospital Los Angeles have discovered a link between predispositions to obesity and formation of brain connections that likely impact weight regulation and appetite later in life.  The research was conducted in the Neuroscience Program of The Saban Research Institute.  Results of this study will be reported in the February 6, 2008 issue of the journal Cell Metabolism.
    The cover article, titled, “Hypothalamic neural projections are permanently disrupted in diet-induced obese rats,” documents the surprising finding that rats genetically predisposed to develop obesity display marked differences in development of the brain circuits that are known to regulate appetite and body weight.
    The researchers studied two types of rats: obesity-prone rats and obesity-resistant (lean) rats.
    “Our results suggest that the development of the brain connections controlling feeding and body weight regulation is comprised in individuals predisposed to develop obesity, as compared to obesity-resistant individuals,” said Richard B. Simerly, Ph.D., director of the Neuroscience Program at The Saban Research Institute of Childrens Hospital Los Angeles and a professor of pediatrics at the Keck School of Medicine of the University of Southern California.
    Their work is based on an earlier finding that a hormone called leptin influences brain development. Leptin is a fat-derived hormone that acts on the brain to reduce food intake in adults.  In newborns, it acts as a neurotrophic growth factor to promote the normal innervation of brain regions controlling hunger.
    Specifically, the scientists wanted to determine if the changes in brain wiring observed in obesity-prone animals were due to reduced ability of leptin to promote brain development.
    “We found that the neurodevelopmental abnormalities observed in these animals are due to reduced responsiveness of specific neurons to the growth-promoting actions of leptin that normally occurs during postnatal life,” said Sebastien G. Bouret, Ph.D., a co-investigator, also in the Neuroscience Program at The Saban Research Institute of Childrens Hospital Los Angeles and an assistant professor of pediatrics at the Keck School of Medicine.
    According to Drs. Bouret and Simerly, these findings imply that one way for polygenic backgrounds to predispose individuals to diet-induced obesity may be through alterations in how the brain responds to endocrine signals early in life, with enduring consequences for appetite and weight regulation.
    In addition to his position with The Saban Research Institute, Dr. Bouret is a researcher at the French National Institute of Health, Unit 837, in Lille, France.
    Drs. Simerly and Bouret have been invited to lecture internationally, including in Canada, France, Holland, Italy, Japan, Spain, Sweden, Switzerland and in the United Kingdom.
    Founded in 1901, Childrens Hospital Los Angeles has been treating the most seriously ill and injured children in Los Angeles for more than a century, and it is acknowledged throughout the United States and around the world for its leadership in pediatric and adolescent health. Childrens Hospital is one of America’s premier teaching hospitals, affiliated with the Keck School of Medicine of the University of Southern California since 1932.  It is a national leader in pediatric research.